CASE REPORT Open Access

Melkerrson-Rosenthal Syndrome, a rare casereport of chronic eyelid swellingBabita Kajal1*, John Harvey2 and Salem Alowami1

Abstract

Melkerrson-Rosenthal syndrome is a rare disorder of unknown etiology. The classical triad of recurrent facialparalysis, swelling of the face, lips and deep furrowed tongue (Lingua Plicata) is seen in very few cases, majority ofthe patients often present with one or two symptoms only, which often leads to misdiagnosis andmismanagement. Clinically these symptoms vary from days to years, which further delay the definitive diagnosisand symptoms may eventually become permanent. The cause of this entity is not very well understood, butthought to be attributable to multiple entities including genetic and Infectitious. As this entity has been associatedwith numerous other clinical entities, diagnosis often remains an exclusion process. Methods: A middle age malewith a chronic history of heavy eyelids with skin indurations predominately around left eye was presented toophthalmology clinic. Physical examination revealed a deep furrowed tongue. The skin biopsy from left eyelidrevealed a non-specific granulomatous lesion. The clinical correlation of facial swelling and deep plicated tongueprompted the differential of MRS. Results: Histologically a non-specific granulomatous lesion was seen in dermis. Asa rule, other causes of granulomatous diseases were ruled out especially Crohn’s disease and sarcoidosis.Polarization failed to reveal any foreign body. Conclusions: The finding of granulomatous lesion and clinicalpicture led to the definite diagnosis of Melkerrson-Rosenthal syndrome. Association with rosacea was otherfindings. Clinically his sign and symptoms are under control and no occurrence of symptoms has been notedso far.Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1647494495993706

Keywords: Melkerrson Rosenthal syndrome, Granulomatous disease

BackgroundMelkerrson Rosenthal syndrome is a rare neurologicaldisorder characteristically shows swelling of face, lips, fa-cial paralysis and deep plicated tongue [1]. This classicaltriad is not seen in all of the patients, majority of thepatients often show one or two features only. Durationof sign and symptoms also adds to clinical dilemma asthese symptoms may vary from days to years, whicheventually become chronic enough to cause permanentdisfigurement of the facial part involved. Cheilitis granu-lomatous of Miescher is considered as monosymptomaticform of MRS. This entity has worldwide distribution andequally involves both genders. The definite etiology is still

unknown. Despite the factor that numerous studies havebeen done to prove it as genetic or infectious entity, thisremains a diagnosis of exclusion. Autosomal dominancehas been proposed in few cases with chromosomal in-volvement of 9p11. Association of MRS has been seenwith many other clinical entitles. Histological examinationreveals a nonspecific granulomatous lesion with dermaledema and perivascular lymphocytic infiltrate. As in anygranulomatous lesions, differential list is very exhaustive.Crohn’s and sarcoidosis needs to be ruled out first, asthese diseases may co express or may develop during thecourse of MRS [2,3]. Histologically granulomas may notbeen seen in all cases, but that does not rule out the diag-nosis of MRS. The granulomatous reaction and clinicalfindings of eyelids swelling, deep furrowed tongue oftenhelps in the definite diagnosis of Melkerrson Rosenthalsyndrome. Patient may respond to steroids and other

* Correspondence: babita.kajal@medportal.ca1Department of pathology and molecular medicine, McMaster University,1280 Main street west, Hamilton, Ontario L8N 3Z5, CanadaFull list of author information is available at the end of the article

© 2013 Kajal et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

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immunosuppressants. Clinically high suspicion index isrequired to solve this clinical quandary.

Case reportA 51-year-old male presented with clinical symptoms ofbilateral heavy lids, predominantly on left side of one-year duration. No itchiness, no redness was found.Working clinical diagnosis of allergy, facial rosacea, orblepharocalasis was made. A 3 mm punch biopsy takenfrom left lid swelling and submitted for histopathologicalexamination. His past medical history include hernia re-pair, left knee scope for benign cyst, left shoulder repair.Family history was remarkable for colon cancer, but col-onoscopy was normal for patient. No other significantmedical history given in chart. In our departmentwe received a left eye lesion skin biopsy, measuring0.3x0.3x0.3 cm, submitted in one block. Microscopicsections revealed unremarkable epidermis with milddegree of hyperkeratosis. Underlying dermis showededema, perivascular lymphocytic infiltrate and welldefined perilymphatic non- necrotizing granulomas.Descriptive diagnosis of “edema with mild chronic in-flammation and focal perilymphatic granulomas” wasgiven (Figures 1, 2, 3). Fungal, bacterial and mycobacter-ium stains were negative. Polarization failed to revealforeign body. The diagnosis of MRS was suggested basedupon chronic eyelids swelling and deep plicated tongue(Figures 4 and 5). The serology was negative for cANCA, p ANCA, angiotensin converting enzyme, andcyclic citrullinated peptide antibody. Patient was startedon steroid therapy and doxycycline, patient respondedexcellent for both eyelid swelling and rosacea.

DiscussionMelkerrson Rosenthal syndrome is a rare neurologicalentity of unknown etiology. Classical triad includes re-current facial palsy, swelling of lips, and deep furrowedtongue (lingua plicata, sometimes known as scrotal

tongue, but these classical findings are seen rarely [4].Majority of the patient has one or two symptoms onlyrather than classical triad as mentioned above. MRS hasconsiderable overlap or rather confusing terminology,especially when classical triad is not seen. Mieschercheilitis may be a monosymptomatic form of theMelkerrson-Rosenthal syndrome, but probably these aretwo separate entities. Approximately 86% of the casespresent with orofacial swelling and furrowed tongue arealmost present congenitally [5]. Fissured and woodytongue may also be seen in other conditions includinglipoid proteinosis, which is a rare autosomal recessivedisorder characterized by deposition of PAS positive ma-terial in various organ systems and is caused by loss offunction mutation in gene encoding ECM1 (extracellularmatrix protein 1) on chromosome 1q21 [6]. In availableliterature, there is no ECM 1 protein abnormality seenin MRS. The term MRS used only when cheilitis occurswith facial palsy and deep furrowed tongue. The term

Figure 1 Dermal edema, peri-lymphatic infiltrate and nonca-seating granuloma.

Figure 2 Non caseating granuloma.

Figure 3 Higher power, non caseating granuloma.

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orofacial granulomatosis (OFG) is used when there is nounderlying Crohn, s disease. This entity is seen equallyin both gender and has worldwide distribution. Due toinconsistency of sign and symptoms appearance andduration of symptoms, majority of patient’s goes undiag-nosed for long period of time, as long as for 30 years,and may eventually become permanent [7]. Recurrentswelling of eyes and upper lip usually involves the sameside. The facial palsy is notably seen in the region ofVIIth nerve distribution, which can be mistaken clinic-ally as Bells palsy. Severity of palsy also may vary frommild to severe, which could be unilateral or bilateral. In-volvement of other cranial nerves also has beennoted such as olfactory auditory; glossopharyngeal andhypoglossal nerves [8]. Numbness can involve otherbody parts also.Regarding pathogenesis this is not a well understood

entity, multiple attempts to prove this entity as inher-ited/ acquired/ neurological or immunological has yieldno conclusive data. Many authors associate this syn-drome with some form of herpes infection, otherconsider as an immunological response to multiple cir-culating antigen which leads to allergic granulomatous

reaction. Many factors are thought to attribute to eti-ology namely genetics and infections particularity oralcandidiasis and mycobacterium. Other etiologies underconsideration are autoimmune factors, hypersensitivityand neurotrophic factors, which leads to vasomotordisturbances causing numbness. Deficiency of comple-ment C1-INH may be the etiological factor contributingto orofacial swelling [9]. DNA sequence study ofMAP1S900 (Mycobacterium avium subspecies paratu-berculosis (MAP) has been found in few studies [10,11].In another case study, attempt to find borrelia burgdor-feri a spirochete as an etiological agent did not revealany positive results [12].An autosomal dominant inheritance with variable ex-

pression has been proposed in some cases of MRS andde-novo translocation of t (9; 21) (p11; p11) has seen inmany cases [13]. Seven family members of four genera-tions have been described forming the genetic basis ofthis entity [14]. Attempt to study the blood DNA forUNC-93B1 gene mutations predisposing to herpes virusinfection in patients of MRS with facial palsy yield no re-sults [15]. Is this a clonal disorder of T lymphocytes re-mains to be determined? [16]. So far there are manyspeculations about the pathogenesis, but without anydefinite conclusions.MRS with facial palsy of Melkerrson syndrome may

present alone or as a disease spectrum of various otherunderlying diseases, such as association has been seen inmany other chronic diseases including diabetic mellitus[17], Crohn’s disease [18]. Ehler –Danlos syndrome [19],Psoriasis [20], Crocodile Tear syndrome [21], Rosacea[22], Hashimoto thyroditis [23], Leprosy [24] and Downsyndrome [25]. Hereditary Melkerrson Rosenthal syn-drome and multiple sclerosis has been noted in one fam-ily [26]. The term MRS is used only when there is noother underlying etiology.A retrospective diagnosis of total 72 biopsied cases

was done at mayo clinic and concluded it as a chronicdisease that may present over the course of most of thelifespan and may require several years of observation tobe diagnosed. Neurologists who observe a combinationof facial edema and facial palsy in a patient should con-sider the diagnosis of MRS and proceed to a diagnosticskin biopsy and a trial of steroid treatment for theirpatient [27]. Melkerrson-Rosenthal syndrome shouldbe suspected in cases of recurrent facial palsy associatedwith swelling of orofacial structures and furrowedtongue [28].Histologically non-caseating granulomas are seen in

dermis. Other findings included perivascular inflamma-tory infiltrate and dermal edema. The granulomas maybe seen around lymphatic and blood vessels [29]. Fewof the cases might not show any granulomas, but lym-phangiectasia and perivascular lymphocytic infiltrate

Figure 4 Eye lid swelling.

Figure 5 Deep plicated tongue.

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only. This is a diagnosis of exclusion as extensive labora-tory and clinical work up is required to rule in and ruleout various other immunological or non-immunologicalconditions.Differential diagnosis of MRS includes thyroid retinop-

athy, allergy, atophy, angioedema, bacterial, viral or filarialinfections, systemic lupus erythematosus, dermatomyositis,bell’s palsy, leprosy and rosacea. Non-caseating granulomasin biopsies is a nonspecific finding which further requires adetailed workup.As MRS is a chronic disorder of relapses and remis-

sions, main emphasis of treatment is symptomatic torelieve the swelling and pressure symptoms. Many treat-ment options include steroids, immunosuppressant ther-apy, and reconstructive surgery [30,31]. In follow-upcare, one must exclude the development or coexistenceof Crohn’s disease or sarcoidosis.

ConclusionsMRS is a disease spectrum which might co express withmany other clinical entities. Our emphasis is on the skil-ful and detailed workup between treating physician insolving the diagnostic quandary of this rare and confus-ing entity. We conclude that Melkerrson - Rosenthalsyndrome should in the differential diagnosis of orofacialswelling and fissured tongue. Our patient responded wellto prednisone and doxycycline [32].

ConsentWritten informed consent was obtained from the patientfor the publication of this report and any accompanyingimages.

AbbreviationMRS: Melkerrson- Rosenthal Syndrome.

Competing interestsThe authors declare that they have no competing interests.

Authors’ contributionsBK drafted the manuscript and collected data; SA analyzed histopathologicalsections and correlated with clinical findings. JH provided the clinical details;written consent and treatment follow up of the patient. All authors read andapproved the final manuscript.

Author details1Department of pathology and molecular medicine, McMaster University,1280 Main street west, Hamilton, Ontario L8N 3Z5, Canada. 2Department ofophthalmology, McMaster University, 1280 Main street west, Hamilton,Ontario L8N 3Z5, Canada.

Received: 14 May 2013 Accepted: 30 October 2013Published: 13 November 2013

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doi:10.1186/1746-1596-8-188Cite this article as: Kajal et al.: Melkerrson-Rosenthal Syndrome, a rarecase report of chronic eyelid swelling. Diagnostic Pathology 2013 8:188.

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